The present invention relates to a new use for a known compound, thalidomide. Thalidomide has been known as a tranquilizer since the late 1950's. The compound thalidomide was patented in Keller, U.S. Pat. No. 2,830,991 issued Apr. 15, 1958. It has the chemical name 3-phthalimido-piperidine dione 2,6. Thalidomide is a derivative of glutamic acid.
As is well known, thalidomide was widely used in the early 1960's as a tranquilizer in Europe, although never approved for use in the United States. When it was discovered that even small amounts of thalidomide when taken by pregnant women caused birth defects, the drug was rapidly withdrawn from the market. As a result, thalidomide was never approved for use in the United States. Since that period in the early 1960's researchers have found that thalidomide is useful in treating inflammation associated with severe cases of erythema nodosum leprosum (ENL) leprosy. There is also literature indicating that the drug is useful in treating inflammatory processes associated with for example Lupus, see Lo, et al., treatment of discoid Lupus erythematosus, International Journal of Dermatology, October 1989 Vol. 29, No. 8, p. 497-507.
At this point it is beyond question that thalidomide when taken by pregnant women is a teratogen; however, the fact remains that sufficient scientific evidence exists to merit its investigation for uses in environments in which it will not have the opportunity to function as a teratogenic agent. For example, thalidomide is now widely used in treatment of leprosy in situations where there is no risk to females of child bearing potential.
In summary, thalidomide is known to have sedative and hypnotic effects and to be useful in treating Lupus and leprosy. Care must be taken, however, when thalidomide is used, to avoid systemic use in females of child bearing potential.
Recognizing this limitation of thalidomide, but also the potential value of the drug, a research project was begun to determine whether or not a technique could be developed to take advantage of uses of thalidomide without significant risk of its teratogenic effects. In this regard investigations were commenced into possible uses of thalidomide as a topical treatment, the theory being that if used topically as opposed to systemically, advantages of the drug could be used without the disadvantages.
In commencing such investigations the research was compounded in difficulty by the fact that thalidomide, its pro drugs and analogues are difficultly soluble at best. This lack of solubility creates special formulation problems for topicals, since an effective topical composition must have satisfactory percutaneous absorption levels in order to be effective.
Accordingly, it is the primary object of the present invention to prepare effective solubilized and/or suspended topical compositions of thalidomide useful for treating skin ulcerations and lesions.
Another objective of the present invention is to provide ointments, creams, lotions, solutions, mucosal dosage forms, and skin pharmaceutical compositions effective for treating skin and mucosal ulcerations and lesions, which compositions contain as their active solubilized or suspended thalidomide.
Another objective of the present invention is to provide thalidomide in a delivery system which can be used for topical treatment without causing adverse systemic effects.
Another objective of the present invention is to provide thalidomide in a delivery system which can be used for ophthalmic treatment without causing adverse systemic effects.
Still another objective of the present invention is to provide enhanced solubilization and/or suspension of thalidomide in dimethyl sulfoxide in a composition suitable for topical treatment without adverse systemic effects.
The method and means of accomplishing each of the above objectives as well as others will become apparent from the detailed description of the invention which follows hereinafter.